Quantum dots (qdots) have emerged as new fluorescent, non-isotopic labels that are thought to have unmatched potentials as novel intravascular probes for both diagnostic (e.g., biological imaging) and therapeutic purposes (e.g., drug delivery). This application capitalizes on the progress we have made in the first 5 years of BRP funding, aiming to bring qdots one step closer to routine use in pre-clinical and clinical models. Towards this goal, we will perform detailed validation studies of targeted qdots in living mice models that are already impacting clinical management of cancer patients by using small animal imaging technologies including multiphoton microscopy and fluorescence tomography. During the next 5 years of this project, we will (1) develop and bioconjugate new multimodal contrasting qdot agents;(2) develop new optical instruments for near infrared (NIR) qdot detection and (3) perform validation studies of targeted qdots in cells and animals. We will focus on cancer where no single imaging agent can provide adequate information for diagnosis, prognosis and treatment decisions. Rather, a better understanding of the biological behavior and potential of malignant cells is inherent to new instrumentations and probes that will allow multiplex imaging of panels of targets/markers. The availability of NIR qdots with several output wavelengths, coupled with tumor marker-specific engineered antibodies, peptides or nucleic acids, will streamline multicolor/ marker imaging of cells and tumors. We will develop panels of qdot probes useful for karyotyping cancerous cells and for gene expression profiling towards a combination of genes that would be diagnostic or prognostic markers for cancer progression. Using cancer models, we will visualize the bio-distribution of qdots at all scales, from the level of the whole animal body down to nanometer resolution using a single probe by combining the micro-PET and optical modalities of antibody-functionalized NIR qdots. We will also asses toxicity and size effects on biodistribution of these probes. Our multidisciplinary team of 5 investigators with expertise in physics, chemistry, materials sciences, bioengineering, pharmacology, imaging and cancer biology should help to more rapidly validate this new exciting class of imaging probes for eventual clinical applications. Lay abstract: Physicians can now monitor tumors and malignant cells deep within our body. Our research aims at validating new sensitive probes (known as Quantum Dots, or qdots) for non-invasive tumor imaging in animal models. The unique properties of qdots might afford in the future earlier diagnosis and better management of disease in humans.